The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal

Background: Serum carbohydrate antigen (CA 19-9) is the most common tumor marker assessed in pancreatic cancer patients; nevertheless few articles have comprehensively evaluated the evidence for its utility in pancreatic cancer management. Methods: Literature search was performed using Medline with keywords "pancreatic cancer" "tumor markers" "CA 19-9" "diagnosis" "screening" "prognosis" "resectability" and "recurrence". All English language articles pertaining to the role of CA 19-9 in pancreatic cancer were critically analyzed to determine its utility as a biomarker for pancreatic cancer. Results: Serum CA 19-9 is the most extensively validated pancreatic cancer biomarker with multiple clinical applications. CA 19- 9 serum levels have a sensitivity and specificity of 79-81% and 82-90% respectively for the diagnosis of pancreatic cancer in symptomatic patients; but are not useful as a screening marker because of low positive predictive value (0.5-0.9%). Pre-operative CA 19-9 serum levels provide useful prognostic information as patients with normal levels (< 37 U/mL) have a prolonged median survival (32-36 months) compared to patients with elevated levels (>37 U/mL) (12-15 months). A CA 19- 9 serum level of < 100 U/mL implies likely resectable disease whereas levels > 100 U/mL suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19- 9 serum levels by >= 20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19- 9 serum levels to normalize or an increase. Important limitations to CA 19- 9 serum level evaluation in pancreatic cancer include poor sensitivity, false negative results in Lewis negative phenotype (5-10%) and increased false positivity in the presence of obstructive jaundice (10-60%). Conclusions: CA 19- 9 is the most extensively studied and validated serum biomarker for the diagnosis of pancreatic cancer in symptomatic patients. CA 19- 9 serum levels can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. However, non-specific expression in several benign and malignant diseases, false negative results in Lewis negative genotype and an increased false positive results in the presence of obstructive jaundice severely limit the universal applicability of serum CA 19-9 levels in pancreatic cancer management.